December 5, 2012
More Drugs Than Ever Can Dangerously Interact
With Grapefruit

London, Ontario—More than 20 years ago, researchers warned health care professionals that grapefruit could have dangerous interactions with prescription drugs. Now, the number of prescription drugs that can have serious adverse effects when combined with grapefruit is increasing, but awareness has not kept pace.

That’s according to a new review published in CMAJ (Canadian Medical Association Journal) by the researchers who discovered the interactions more than 2 decades ago.

“Many of the drugs that interact with grapefruit are highly prescribed and are essential for the treatment of important or common medical conditions,” writes David Bailey, PhD, of the Lawson Health Research Institute in London, Ontario, with coauthors. “Recently, however, a disturbing trend has been seen. Between 2008 and 2012, the number of medications with the potential to interact with grapefruit and cause serious adverse effects…has increased from 17 to 43, representing an average rate of increase exceeding 6 drugs per year. This increase is a result of the introduction of new chemical entities and formulations.”

While some adverse effects can be mild, others can be extremely serious, even deadly. Among those are sudden death, acute kidney failure, respiratory failure, gastrointestinal bleeding, bone marrow suppression in immunocompromised patients, and renal toxicity.

“Unless health care professionals are aware of the possibility that the adverse event they are seeing might have an origin in the recent addition of grapefruit to the patient’s diet, it is very unlikely that they will investigate it,” the authors write. “In addition, the patient may not volunteer this information. Thus, we contend that there remains a lack of knowledge about this interaction in the general healthcare community.”

The article noted that more than 85 drugs can interact with grapefruit, with 43 having the potential for serious side effects. Among those are atorvastatin and other common heart medications—including verapamil and amiodaron.

Simvastatin, for example, produced a 330% systemic concentration of the drug when combined with a 200-mL glass of grapefruit juice once a day for 3 days, compared with water, according to the review.

The effect is not limited to grapefruit. Other less-sweet citrus fruits such as Seville oranges, limes, and pomelos also contain the active ingredients furanocoumarins. Those cause the interaction by irreversible inhibition of the drug metabolizing CYP3A4 enzyme that normally inactivates the effects of an estimated 50% of all medication.

According to the study, drugs that interact with these chemicals have three characteristics:

• Oral administration;
• Low-to-intermediate bioavailability; and
• Drug metabolism in the gastrointestinal tract by CYP3A4.

The review notes that, for drugs with very low bioavailability, one-time ingestion of a normal amount of grapefruit can be analogous to consuming multiple doses of the drug alone. In fact, the authors note, as little as one grapefruit or one 8-ounce glass of grapefruit juice can cause an effect that may last more than 24 hours. Frequent daily consumption of a regular amount can heighten the effect.

The review notes that consumers of grapefruits tend to be older than 45—an age group that also is more likely to have drug prescriptions.

“The current trend of increasing numbers of newly marketed grapefruit-affected drugs possessing substantial adverse clinical effects necessitates an understanding of this interaction and the application of this knowledge for the safe and effective use of drugs in general practice,” the authors conclude.

U.S. Pharmacist Social Connect